A mechanistic modelling approach of the host–microbiota interactions to investigate beneficial symbiotic resilience in the human gut

Abstract

The health and well-being of a host are deeply influenced by the interactions with its gut microbiota. Contrasted environmental conditions, such as diseases or dietary habits, play a pivotal role in modulating these interactions, impacting microbiota composition and functionality. Such conditions can also lead to transitions from beneficial to detrimental symbiosis, viewed as alternative stable states of the host–microbiota dialogue. This article introduces a novel mathematical model exploring host–microbiota interactions, integrating dynamics of the colonic epithelial crypt, microbial metabolic functions, inflammation sensitivity and colon flows in a transverse section. The model considers metabolic shifts in epithelial cells based on butyrate and hydrogen sulfide concentrations, innate immune pattern recognition receptor activation, microbial oxygen tolerance and the impact of antimicrobial peptides on the microbiota. Using the model, we demonstrated that a high-protein, low-fibre diet exacerbates detrimental interactions and compromises beneficial symbiotic resilience, underscoring a destabilizing effect towards an unhealthy state. Moreover, the proposed model provides essential insights into oxygen levels, fibre and protein breakdown, and basic mechanisms of innate immunity in the colon and offers a crucial understanding of factors influencing the colon environment.